II. Indications

III. Contraindications

IV. Mechanism

  1. Anti-Folate agent active as an antineoplastic and Immunosuppressant
  2. Targets cells expressing RFC-1 (reduced Folate carrier-1)
  3. Folate analog inhibitor of dihydrofolate reductase (DHFR)
    1. Blocks Tetrahydrofolate synthesis
    2. Depletes Nucleotide precursors
    3. Inhibits DNA, RNA and Protein synthesis

V. Medications

  1. Pralatrexate IV Solution 20 mg/ml in 1 to 2 ml vials

VI. Dosing

  1. See other references for disease specific dosing protocols
  2. Adult: 30 mg/m2 IV once weekly for 6 weeks, followed by 1 week of no Pralatrexate
  3. Coadministered agents to reduce adverse effects (e.g. mucositis)
    1. Folic Acid 1 to 1.25 mcg orally daily
      1. Start 10 days before, and continue for 30 days after last Pralatrexate dose
    2. Vitamin B12 1000 mcg IM
      1. Give one dose within 10 weeks of starting Pralatrexate
      2. Repeat Vitamin B12 dosing every 10 weeks while taking Pralatrexate

VII. Adverse Effects

  1. Hepatotoxicity
  2. Myelosuppression
  3. Mucositis
  4. Life-Threatening Drug-Induced Rashes (e.g. Toxic Epidermal Necrolysis)

VIII. Safety

  1. Avoid in Pregnancy (any trimester)
    1. Use reliable Contraception
  2. Avoid in Lactation

IX. Drug Interactions

  1. Drugs that prolong Pralatrexate activity (decreased clearance)
    1. NSAIDs
    2. Trimethoprim Sulfamethoxazole

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Ontology: Pralatrexate (C1721300)

Definition (NCI) A folate analogue inhibitor of dihydrofolate reductase (DHFR) exhibiting high affinity for reduced folate carrier-1 (RFC-1) with antineoplastic and immunosuppressive activities. Pralatrexate selectively enters cells expressing RFC-1; intracellularly, this agent is highly polyglutamylated and competes for the folate binding site of DHFR, blocking tetrahydrofolate synthesis, which may result in depletion of nucleotide precursors; inhibition of DNA, RNA and protein synthesis; and apoptotic tumor cell death. Efficient intracellular polyglutamylation of pralatrexate results in higher intracellular concentrations compared to non-polyglutamylated pralatrexate, which is more readily effuxed by the MRP (multidrug resistance protein) drug efflux pump. RFC-1, an oncofetal protein expressed at highest levels during embryonic development, may be over-expressed on the cell surfaces of various cancer cell types.
Definition (NCI_NCI-GLOSS) A drug used in the treatment of peripheral T-cell lymphoma (a fast-growing form of non-Hodgkin lymphoma). It is also being studied in the treatment of other types of cancer. Pralatrexate may block the growth of cancer cells and cause them to die. It is a type of dihydrofolate reductase (DHFR) inhibitor.
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH C418863
SnomedCT 429320009, 428598004
English Pralatrexate (product), Pralatrexate (substance), pralatrexate, Pralatrexate, PRALATREXATE, PRALAtrexate
Spanish pralatrexato (sustancia), pralatrexato (producto), pralatrexato